中文摘要：

目的 研究左旋多巴诱发异动症（levodopa-induced dyskinesias，LID）大鼠纹状体内前强啡肽原（prodynorphin，PDyn）基因表达与DARPP-32蛋白磷酸化状态的变化，探讨LID时直接通路过度活化的机制。方法 6-羟多巴胺（6-OHDA）大鼠模型应用左旋多巴治疗28d诱发LID大鼠模型。采用原位杂交技术检测PDyn mRNA水平，逆转录-聚合酶链反应（RT-PCR）及免疫印迹技术检测LID大鼠纹状体内总DARPP-32的mRNA与蛋白表达及其Thr-34位点磷酸化水平。结果 LID大鼠毁损侧PDyn mRNA表达（0．3662±0．0625）较对照组（0．2085±0．0573）及L-dopa治疗组（0．2235±0．0582）明显增高，差异有统计学意义（P〈0．01）。LID大鼠毁损侧Thr-34位点磷酸化的DARPP-32蛋白水平（1075．2±103．3）较对照组（198．7±49．5）及L-dopa治疗组（213．9±58．9）明显增高，差异均有统计学意义（P〈0．01）。结论 DARPP-32蛋白的Thr-34位点的磷酸化水平的改变是LID时多巴胺D1受体介导的直接通路异常活化的关键因素之一。

英文摘要：

Objective To study the changes of prodynorphin （PDyn） gene expression and dopamine and cAMP-regulated phosphoprotein （ DARPP-32 ） phosphorylation and to explore the mechanism of overactivation in direct-pathway in rats with levodopa-induced dyskinesias（LID）. Methods 6-OHDA rat models received twice levodopa celiac （ 10 mg/kg） injections daily for 28 days to get LID rats. The normal rats received same course and dosage of levodopa as a control group. Hybridization in situ was used to measure the expression of PDyn mRNA in striatum. Protein and mRNA levels of total DARPP-32 and phospho-Thr-34 DARPP-32 levels were measured by immunoblotting and reverse transcriptase-polymerase chain reaction （ RT-PCR）, respectively. Results The levels of PDyn mRNA in LID group （ 0. 3662 ± 0. 0625 ） was increased significantly compared to those of control （ 0. 2085 ± 0. 0573 ） and levodopa treatment group （0. 2235 ± 0. 0582 ） （ P 〈 0. 01, respectively ） . Phospho-Thr-34 DARPP-32 expression in LID group （ 1075. 2 ± 103.3 ） increased significantly compared to controls（ 198.7 ± 49. 5 ） and levodopa treatment group （ 213.9 ± 58.9） （ P 〈 0. 01, respectively）. Conclusion Phospho-Thr-34 DARPP-32 level is increased in LID rats, which contributes to the over-activation in direct-pathway.